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M Schachner

Publications and source records attributed to M Schachner.

At least 109 records · Page 6Linked to original sources
PubMed1998

Differential effects of autologous peripheral nerve grafts to the corpus striatum of adult rats on the regeneration of axons of striatal and nigral neurons and on the expression of GAP-43 and the cell adhesion molecules N-CAM and L1.

A segment of tibial nerve was autografted to the right corpus striatum of deeply anesthetized adult rats; the distal graft was left beneath the scalp. Horseradish peroxidase (HRP) conjugates were injected into the distal graft after 2-30 weeks, and the animals were killed 2-3 days later. Small numbers of neostriatal perikarya were HRP labeled at all survival times; most were large (ca. 20 microm in diameter), and many contained acetycholine esterase (AChE). Many more neurons were labelled in the substantia nigra pars compacta (SNpc) 4 weeks or more after grafting. When the graft encroached on the globus pallidus, numerous pallidal neurons, most of them AChE positive, were also labeled. Nigrostriatal neurons, a population of pallidal cholinergic neurons, and a subclass (or classes) of neostriatal neurons, including cholinergic interneurons, thus can be classified as central nervous system (CNS) neurons with a relatively strong regenerative response. In a second experimental series, animals were killed 1-4 weeks after grafting, and sections were probed for the expression of mRNAs encoding growth-associated protein 43 (GAP-43) and the cell adhesion molecules N-CAM and L1. Subpopulations of mostly large neurons scattered throughout the neostriatum gave moderate signals for GAP-43 and N-CAM mRNAs and a stronger signal for L1 mRNAs. Most SNpc neurons were strongly labeled with all three probes. Neostriatal grafts had no apparent effect on the expression of any of the mRNAs in the SNpc or on L1 and N-CAM mRNAs in the striatum. However, GAP-43 mRNA levels were increased in a few, mainly large neostriatal neurons around the graft tip, resembling the HRP-labeled cells. In contrast, previous work has shown upregulation (from an undetectable level) of GAP-43 and L1 mRNAs in neurons regenerating axons into grafts placed in the thalamus and cerebellum. Thus, GAP-43 and L1 mRNA expression, but not necessarily marked upregulation, may correlate with, and be intrinsic determinants of, the ability of CNS neurons to regenerate their axons.

Acetylcholinesterase↗
PubMed1998

Potassium channel distribution, clustering, and function in remyelinating rat axons.

The K+ channel alpha-subunits Kv1.1 and Kv1.2 and the cytoplasmic beta-subunit Kvbeta2 were detected by immunofluorescence microscopy and found to be colocalized at juxtaparanodes in normal adult rat sciatic nerve. After demyelination by intraneural injection of lysolecithin, and during remyelination, the subcellular distributions of Kv1.1, Kv1.2, and Kvbeta2 were reorganized. At 6 d postinjection (dpi), axons were stripped of myelin, and K+ channels were found to be dispersed across zones that extended into both nodal and internodal regions; a few days later they were undetectable. By 10 dpi, remyelination was underway, but Kv1.1 immunoreactivity was absent at newly forming nodes of Ranvier. By 14 dpi, K+ channels were detected but were in the nodal gap between Schwann cells. By 19 dpi, most new nodes had Kv1.1, Kv1.2, and Kvbeta2, which precisely colocalized. However, this nodal distribution was transient. By 24 dpi, the majority of K+ channels was clustered within paranodal regions of remyelinated axons, leaving a gap that overlapped with Na+ channel immunoreactivity. Inhibition of Schwann cell proliferation delayed both remyelination and the development of the K+ channel distributions described. Conduction studies indicate that neither 4-aminopyridine (4-AP) nor tetraethylammonium alters normal nerve conduction. However, during remyelination, 4-AP profoundly increased both compound action potential amplitude and duration. The level of this effect matched closely the nodal presence of these voltage-dependent K+ channels. Our results suggest that K+ channels may have a significant effect on conduction during remyelination and that Schwann cells are important in K+ channel redistribution and clustering.

4-Aminopyridine↗
PubMed1998

Anterior-posterior subdivision of the somite in embryonic zebrafish: implications for motor axon guidance.

The ventral branches of the segmental peripheral nerves in the zebrafish embryo are pioneered by the caudal primary (CaP) motor axons, which extend midsegmentally at the interface of the somite and the notochord. The signals that define the CaP pathway are not well understood. To gain insight into the nature of the guidance cues, we have examined the environment of the CaP motor axons by using electron microscopy and histochemistry. Specifically, we have mapped the distribution of the transcription factor engrailed, of a chondrotin sulfate epitope, and of the recognition molecules zebrafish semaphorin z1b and zebrafish tenascin C. Ultrastructural examination of dye-labeled CaP motor axons revealed a close association with the medial surface of the somite but not with the notochord. The CaP axons were always accompanied by cells that appeared to migrate at the interface of somite and notochord. These cells were confined to the posterior half of the somite. Some of the cells may be neural crest derived, many others are probably of sclerotomal origin. The putative migratory cells expressed a chondroitin sulfate epitope that is a marker of sclerotome in the chick. The pathway of the CaP axon and the distribution of the putative neural crest and sclerotome cells correlated with a subdivision of the myotome into an anterior and posterior components, which were evident at the histological level and by the expression of the markers engrailed, semaphorin z1b, chondroitin sulfate, and tenascin C. We suggest that both the pathway choice of the CaP axon and the route of migratory cells reflect this anterior-posterior bipartition of the myotome.

Animals↗
PubMed1998

Disruption and reorganization of sodium channels in experimental allergic neuritis.

The axonal distribution of voltage-dependent Na+ channels was determined during inflammatory demyelinating disease of the peripheral nervous system. Experimental allergic neuritis was induced in Lewis rats by active immunization. In diseased spinal roots Na+ channel immunofluorescence at many nodes of Ranvier changed from a highly focal ring to a more diffuse pattern and, as the disease progressed, eventually became undetectable. The loss of nodal channels corresponded closely with the development of clinical signs. Electrophysiological measurements and computations showed that a lateral spread of nodal Na+ channels could contribute significantly to temperature sensitivity and conduction block. During recovery new clusters of Na+ channels were seen. In fibers with large-scale demyelination, the new aggregates formed at the edges of adhering Schwann cells and appeared to fuse to form new nodes. At nodes with demyelination limited to paranodal retraction, Na+ channels were often found divided into two symmetric highly focal clusters. These results suggest that reorganization of Na+ channels plays an important role in the pathogenesis of demyelinating neuropathies.

Animals↗
PubMed1998

Role for cell adhesion and glycosyl (HNK-1 and oligomannoside) recognition in the sharpening of the regenerating retinotectal projection in goldfish.

Cell-adhesion molecules (CAMs) are thought to play crucial roles in development and plasticity in the nervous system. This study tested for a role for cell adhesion and in particular, the recognition of two glycosyl epitopes (HNK-1 and oligomannoside) in the activity-driven sharpening of the retinotopic map formed by the regenerating retinal fibers of goldfish. HNK-1 is a prominent glycosyl epitope on many CAMs and extracellular matrix (ECM) molecules, including NCAM, L1, ependymin, and integrins, which have all been implicated in synaptic plasticity. To test for a role of HNK-1 in the sharpening process, we used osmotic minipumps to infuse HNK-1 antibodies for 7-21 days into the tectal ventricle starting at 18 days after optic nerve crush. Retinotopic maps recorded at 76-86 days postcrush showed a lack of sharpening similar to that seen previously with two antibodies to ependymin, an HNK-1-positive ECM component present in cerebrospinal fluid. The multiunit receptive fields at each point averaged 26 degrees versus 11-12 degrees in regenerates infused with control antibodies or Ringer's alone. The HNK-1 epitope also binds to the G2 domain of laminin to mediate neuron-ECM adhesion. To test for a role for laminin, a polyclonal antibody was similarly infused and also prevented sharpening to approximately the same degree. The results support a role for the HNK-1 epitope and laminin in retinotectal sharpening. The oligomannoside epitope (recognized by monoclonal antibody L3) on the CAM L1 interacts with NCAM on the same cell to promote stronger L1 homophilic interactions between cells. Both an L1-like molecule and NCAM are prominently reexpressed in the regenerating retinotectal system of fish. Infusion of oligomannosidic glycopeptides resulted in decreased sharpening, with multiunit receptive fields that averaged 22.7 degrees. Infusions of mannose-poor glycopeptides less prominently disrupted sharpening, with average multiunit receptive fields of 18 degrees. Thus, oligomannosidic glycans in particular may play a role in retinotopic sharpening. Blocking glycan-mediated interactions between CAMs and ECM molecules could decrease the extent of exploratory growth of retinal axon collaterals, preventing them from finding their retinotopic sites, or could interfere with L1 or NCAM and laminin binding at the synaptic densities preventing stabilization of retinotopically appropriate synapses. Together, these results support a prominent role for cell adhesion and glycan epitopes in visual synaptic plasticity.

Animals↗
PubMed1998

MAG-deficient Schwann cells myelinate dorsal root ganglion neurons in culture.

The myelin-associated glycoprotein (MAG) has been postulated to play a crucial role during myelin formation. Evidence supporting this hypothesis was provided by infecting rat Schwann cells with a retrovirus expressing MAG antisense RNA; these Schwann cells showed reduced levels of MAG expression and failed to myelinate DRG neurons in vitro. However, when MAG expression was disrupted by generating MAG-deficient mice, normal myelin sheaths were formed in peripheral nerves in vivo. In the present study we investigated whether myelination is compromised in MAG-deficient Schwann cells in vitro, i.e., under similar conditions where Schwann cells expressing MAG antisense RNA failed to myelinate. We show that MAG-deficient Schwann cells do myelinate DRG neurons in vitro and express the myelin-specific glycolipid galactocerebroside (Gal-C) and the myelin proteins P0 and MBP. Furthermore, myelin sheaths appear morphologically normal with both compacted and uncompacted aspects when investigated by electron microscopy. Quantitative analysis revealed that the number of myelin sheaths was similar in cultures from MAG-deficient and wild-type mice. These findings support the view that MAG is not essential for myelin formation in the PNS.

Animals↗
PubMed1998

Tyrosine and serine phosphorylation of the neural cell adhesion molecule L1 is implicated in its oligomannosidic glycan dependent association with NCAM and neurite outgrowth.

We have previously shown that a cis interaction between the cell adhesion molecules L1 and NCAM is mediated by N-linked oligomannosidic glycans carried by L1 and that this L1/NCAM association is involved in basal neurite outgrowth from early postnatal cerebellar neurons of mouse brain [R. Horstkorte et al., J. Cell Biol. 121, 1409-1421 (1993)]. Extending these earlier studies we investigated signal transduction mechanisms elicited by this molecular interaction. We show here that phosphorylation of L1 is reduced concomitant with reduced neurite outgrowth when the L1/NCAM interaction is inhibited by oligomannosidic glycopeptides. Similarly, when a peptide of the 4th immunoglobulin (Ig)-like domain of NCAM - representing part of NCAM's carbohydrate-binding site - was added to the culture medium of the cells, neurite outgrowth and phosphorylation of L1 was strongly reduced. No effect on neurite outgrowth and phosphorylation of L1 was observed when cells were maintained in the presence of a peptide comprising part of the 1st Ig-like domain of NCAM or in the presence of the peptide encoded by the variable alternative spliced exon (VASE), which is also located in the 4th Ig-like domain of NCAM. Furthermore, phosphorylation of tyrosine and serine residues of L1 is reduced when the L1/NCAM interaction at the cell surface of cerebellar neurons is perturbed. Our observations suggest that a signal transduction mechanism is implicated in basal neurite outgrowth in which both tyrosine and serine phosphorylation of L1 represent a possible proximal step. Some of these results were presented at the International Glycoconjugate Symposium in Seattle, USA [P. C. Heiland et al., Glycoconj. J. 12, 521(1995)].

Amino Acid Sequence↗
PubMed1998

Cell adhesion molecules in neural plasticity and pathology: similar mechanisms, distinct organizations?

Brain plasticity and the mechanisms controlling plasticity are central to learning and memory as well as the recovery of function after brain injury. While it is clear that neurotrophic factors are one of the molecular classes that continue to regulate brain plasticity in the adult central nervous system (CNS), less appreciated but equally profound is the role of cell adhesion molecules (CAMs) in plasticity mechanisms such as long term potentiation, preservation of neurons and regeneration. Ironically, however, CAMs can also reorganize the extra-cellular space and cause disturbances that drive the development of brain pathology in conditions such as Alzheimer's disease and multiple sclerosis. Candidate molecules include the amyloid precursor protein which shares many properties of a classical CAM and beta-amyloid which can masquerade as a pseudo CAM. Beta-Amyloid serves as a nidus for the formation of senile plaques in Alzheimer's disease and like CAMs provides an environment for organizing neurotrophic factors and other CAMs. Inflammatory responses evolve in this environment and can initiate a vicious cycle of perpetuated neuronal damage that is medicated by microglia, complement and other factors. Certain CAMs may converge on common signal transduction pathways involving focal adhesion kinases. Thus a breakdown in the organization of key CAMs and activation of their signal transduction mechanisms may serve as a new principle for the generation of brain pathology.

Animals↗
PubMed1998

Molecular mechanisms that underlie structural and functional changes at the postsynaptic membrane during synaptic plasticity.

The synaptic plasticity that is addressed in this review follows neurodegeneration in the brain and thus has both structural as well as functional components. The model of neurodegeneration that has been selected is the kainic acid lesioned hippocampus. Degeneration of the CA3 pyramidal cells results in a loss of the Schaffer collateral afferents innervating the CA1 pyramidal cells. This is followed by a period of structural plasticity where new synapses are formed. These are associated with changes in the numbers and shapes of spines as well as changes in the morphometry of the dendrites. It is suggested that this synaptogenesis is responsible for an increase in the ratio of NMDA to AMPA receptors mediating excitatory synaptic transmission at these synapses. Changes in the temporal and spatial properties of these synapses resulted in an altered balance between LTP and LTD. These properties together with a reduction in the inhibitory drive increased the excitability of the surviving CA1 pyramidal cells which in turn triggered epileptiform bursting activity. In this review we discuss the insights that may be gained from studies of the underlying molecular machinery. Developments in one of the collections of the cogs in this machinery has been summarized through recent studies characterizing the roles of neural recognition molecules in synaptic plasticity in the adult nervous systems of vertebrates and invertebrates. Such investigations of neural cell adhesion molecules, cadherins and amyloid precursor protein have shown the involvement of these molecules on the morphogenetic level of synaptic changes, on the one hand, and signal transduction effects, on the other. Further complex cogs are found in the forms of the low-density lipoprotein receptor (LDL-R) family of genes and their ligands play pivotal roles in the brain development and in regulating the growth and remodelling of neurones. Evidence is discussed for their role in the maintenance of cognitive function as well as Alzheimer's. The molecular mechanisms responsible for the clustering and maintenance of transmitter receptors at postsynaptic sites are the final cogs in the machinery that we have reviewed. Postsynaptic densities (PSD) from excitatory synapses have yielded many cytoskeletal proteins including actin, spectrin, tubulin, microtubule-associated proteins and calcium/calmodulin-dependent protein kinase II. Isolated PSDs have also been shown to be enriched in AMPA, kainate and NMDA receptors. However, recently, a new family of proteins, the MAGUKs (for membrane-associated guanylate kinase) has emerged. The role of these proteins in clustering different NMDA receptor subunits is discussed. The MAGUK proteins are also thought to play a role in synaptic plasticity mediated by nitric oxide (NO). Both NMDA and non-NMDA receptors are highly clustered at excitatory postsynaptic sites in cortical and hippocampal neurones but have revealed differences in their choice of molecular components. Both GABAA and glycine (Gly) receptors mediate synaptic inhibition in the brain and spinal cord. Whilst little is known about how GABAA receptors are localized in the postsynaptic membrane, considerable progress has been made towards the elucidation of the molecular mechanisms underlying the formation of Gly receptors. It has been shown that the peripheral membrane protein gephyrin plays a pivotal role in the formation of Gly receptor clusters most likely by anchoring the receptor to the subsynaptic cytoskeleton. Evidence for the distribution as well as function of gephyrin and Gly receptors is discussed. Postsynaptic membrane specializations are complex molecular machinery subserving a multitude of functions in the proper communication between neurones. Despite the fact that only a few key players have been identified it will be a fascinating to watch the story as to how they contribute to structural and functional plasticity unfold.

Animals↗
PubMed1998

Increased immunogold labelling of neural cell adhesion molecule isoforms in synaptic active zones of the chick striatum 5-6 hours after one-trial passive avoidance training.

An area of the chick striatum, the lobus parolfactorius plays an important role in one-trial passive avoidance learning tasks. In the present study we report evidence that 5-6 h post-training, a significantly higher proportion of synaptic active zones in this area contain labelled epitopes of the neural cell adhesion molecule, with the greatest occurrence of labels at the edges of active zone profiles (in both control and trained groups). This suggests that there is a period after training when expression of the neural cell adhesion molecule in synaptic membranes almost doubles, and that events at active zone edges may play a specific role in mechanisms of synaptic adhesion. Cellular mechanisms of long-term memory formation are believed to include alterations in neural circuitry at the synaptic level. The involvement of the neural cell adhesion molecule (NCAM) in functional synaptic modifications has been demonstrated using a number of physiological models. Performance of rats in the Morris water maze, a spatial learning paradigm which requires the hippocampus, is impaired by either intraventricular injection of NCAM antibodies, or injection into the hippocampus of an enzyme which increases homophilic adhesion of the molecule, due to the removal of polysialic acid residuals from extracellular NCAM domains. In addition, intraventricular injections of anti-NCAM antibodies 6-8 h post-training were shown to impair memory for a one-trial passive avoidance task in the rat. An avoidance training model in the one-day-old chick indicates a similar time window, 5-6 h post-training during which memory for the task can be impaired by intraventricular injection of NCAM antibodies. In the hyperstriatum ventrale, a chick forebrain area involved in the passive avoidance task. subtle changes in the distribution pattern, but not density of NCAM molecules in synaptic membranes were revealed 5-6 h post-training. However, on the basis of studies of synaptic morphometry, a region of striatum, the lobus parolfactorius (LPO), appears to play a more important role in longer term memory storage for the task.

Animals↗
PubMed1998

An adhesion test system based on Schneider cells to determine genotype-phenotype correlations for mutated P0 proteins.

Myelin protein zero (MPZ, P0) is well known as the adhesion molecule responsible for the compaction of the myelin sheath of peripheral nerves. Mutations are linked to Charcot-Marie-Tooth syndrome type 1B (CMT1B) and the more severe Dejerine-Sottas syndrome (DSS). Three mutations leading to phenotypes of increasing severity (Ser34del/CMT1B, Ser34Cys/DSS, INS663GC/DSS) were expressed in S2 insect cells and resulted in a decreased adhesion capability in correlation with their respective phenotypes.

Animals↗
PubMed1998

Cytochalasin D disrupts the restricted localization of N-CAM, but not of L1, at sites of Schwann cell-neurite and Schwann cell-Schwann cell contact in culture.

The neural recognition molecules L1 and N-CAM have been shown to be preferentially localized at sites of Schwann cell-to-neurite and Schwann cell-to-Schwann cell contact in vitro. In the present study, we investigated the mechanisms underlying the restricted expression of these molecules at the Schwann cell surface, focusing on the possible role of actin filaments. Co-cultures consisting of Schwann cells from newborn mice and explants of dorsal root ganglia from chicken embryos were maintained in the absence or presence of cytochalasin D, an agent disrupting actin filaments. Immunoelectron microscopy with mouse-specific antibodies was carried out to quantify the restricted localization of L1 and N-CAM at the Schwann cell surface in contact with neurites. After 2 days of co-culturing in the absence of cytochalasin D, approximately 65% of the cell cell contacts showed a restricted immunoreactivity for L1 and N-CAM. The accumulation of L1 at contact sites was unchanged in cytochalasin D-treated co-cultures, while the agent strongly reduced the restricted localization of N-CAM to 20% of all cell-cell contacts. The disruption of N-CAM accumulation appeared to be rapid and occurred within 5 h of cytochalasin D treatment. These results indicate that the restricted localization of N-CAM, but not of L1, is sensitive to cytochalasin D treatment, suggesting a dependence on the integrity of the actin network. Thus, different mechanisms may regulate the subcellular distribution of cell adhesion molecules in Schwann cells.

Actins↗
PubMed1998

Increased flexibility and selectivity in spatial learning of transgenic mice ectopically expressing the neural cell adhesion molecule L1 in astrocytes.

The expression of the neural cell adhesion molecule L1 is altered by neuronal activity and promotes neurite outgrowth in vitro. To study the effects of L1 on learning and synaptic plasticity, transgenic mice have been created which express L1 ectopically in glial fibrillary acidic protein (GFAP) expressing astrocytes. Ninety mice, including GFAP-L1-transgenic mice from two genetic backgrounds and their littermates, were tested for swimming navigation learning in the Morris water maze according to a standardized protocol. While learning the position of an invisible target platform and also relearning its position after relocation, GFAP-L1-transgenic mice spent a greater fraction of their swim time in the target quadrant. Moreover, they showed a more rapid improvement of escape performance during the first day of training. Factor analysis revealed that this difference in swimming pattern could not be explained by non-cognitive factors. Factor analysis also revealed that, during a probe trial, the GFAP-L1-transgenic mice spent comparatively less time in the old target quadrant than predicted by the increased searching they had shown during acquisition learning. Hence, ectopic expression of L1 by astrocytes in mice appears to be linked to a factor which increases behavioural flexibility and selectivity while learning and relearning, but concomitantly may lead to a relative reduction of spatial retention.

Animals↗
PubMed1998

The neural cell adhesion molecule is a receptor for rabies virus.

Previous reports strongly suggest that, in addition to the nicotinic acetylcholine receptor, rabies virus can use other, as-yet-unidentified receptors. We found that laboratory cell lines susceptible to rabies virus infection express the neural cell adhesion molecule (NCAM) (CD56) on their surface, whereas resistant cells do not, supporting the idea that NCAM could be a rabies virus receptor. We observed that (i) incubation with rabies virus decreases the surface expression of NCAM; (ii) treatment of susceptible cells with heparan sulfate, a ligand for NCAM, or with NCAM antibodies significantly reduces the rabies virus infection; and (iii) preincubation of rabies virus inoculum with soluble NCAM protein as a receptor decoy drastically neutralizes the capacity of rabies virus to infect susceptible cells. Moreover, we demonstrated that transfection of resistant L fibroblasts with the NCAM-encoding gene induces rabies virus susceptibility whereas absence of NCAM in the primary cortical cell cultures prepared from NCAM-deficient mice reduces the rabies virus infection and virus production. This provides evidence that NCAM is an in vitro receptor for the rabies virus. Moreover, the in vivo relevance for the use of NCAM as a receptor was demonstrated by the infection of NCAM-deficient mice, in which rabies mortality was delayed and brain invasion by rabies virus was drastically restricted. Our results showed that NCAM, which is expressed mainly in the adult nervous system, plays an important role in rabies infection. However, it cannot be excluded that receptors other than NCAM are utilized. Thus, the description of NCAM as a new rabies virus receptor would be another example of the use by viruses of more than one receptor to gain entry into the host.

Animals↗
PubMed1998

Zebrafish tenascin-W, a new member of the tenascin family.

A cDNA clone encoding tenascin-W, a novel member of the tenascin family, was isolated from a 20- to 28-h postfertilization (hpf) zebrafish cDNA library on the basis of the conserved epidermal growth factor-like domains represented in all tenascin molecules. An open reading frame of 2796 base pairs encodes a mature protein consisting of heptad repeats, a cysteine-rich amino terminal region, 3.5 epidermal growth factor-like repeats, five fibronectin type III homologous repeats, and a domain homologous to fibrinogen. These domains are the typical modular elements of molecules of the tenascin family. Sequence comparison demonstrated that TN-W shares homologies with the members of the tenascin family but is not a species homolog of any identified tenascin. The expression pattern of tn-w was analyzed by in situ hybridization in 1-day-old embryos, in 3-day-old larvae, and in juvenile zebrafish. At 24-25 hpf, tn-w mRNA was expressed in the lateral plate mesoderm, most conspicuously in the presumptive sclerotome. Migrating cells of sclerotomal and neural crest origins also showed high levels of expression. At 3 days, expression by sclerotomal and neural crest cells continued to be observed while expression in the somitic mesoderm was decreased. In juvenile fish, tn-w was expressed weakly by cells in the myosepta and, more strongly, by presumably nonneuronal cells in the dorsal root ganglia. In these tissues and at the same developmental stages, the expression of tn-w partially overlapped with the distribution of tn-c mRNA. In addition, tn-c was expressed in the central nervous system (CNS) and in the axial mesoderm, neither of which expressed tn-w at any of the age stages examined. The expression pattern of tn-w suggests an involvement in neural crest and sclerotome cell migration and in the formation of the skeleton. Similar and possibly overlapping functions could also be performed by tn-c, which appears to have additional functions during the development of the CNS.

Aging↗
PubMed1998

The peripheral nerve and the neuromuscular junction are affected in the tenascin-C-deficient mouse.

A thorough examination of the structure and plasticity of the neuromuscular system was performed in tenascin-C mutant mice deficient in tenascin-C. The study of the peripheral nerve revealed a number of abnormal features. In the motor nerve, numerous unmyelinated and myelinated fibers with degraded myelin were present. Schwann cell processes often enclosed degenerative terminals. Transgene (beta-galactosidase) expression analyzed at the ultrastructural level was found to be unequally distributed in the mutant's neuromuscular tissues. At the NMJ, preterminal disorganization was prevalent. Some axon terminals exhibited abnormal overgrowth. A surprising lack of beta-galactosidase expression at some cellular sites known to possess tenascin-C in wild type mice correlated best with marked changes in the cytoarchitecture of the peripheral nerve and NMJ. In some other -but not all- cellular sites which normally express the molecule, immunofluorescence analysis suggested the presence of significant but low levels of tenascin-C-like immunoreactivity together with beta-galactosidase expression. Messenger RNA detection by RT-PCR confirmed the presence of low amounts of tenascin-C mRNA in skeletal muscle suggesting that the mice deficient in tenascin-C are not complete knock-outs of this gene, but low-expression mutants. Following in vivo injections of botulinum type-A toxin, we observed a greatly reduced sprouting response of the motor nerves in tenascin-C mutant mice. We also observed that N-CAM and beta-catenin were overexpressed in the mutant. Our results suggest that tenascin-C is involved both in stabilization and in plasticity of the NMJ.

Animals↗
PubMed1997

Isolation of a tenascin-R binding protein from mouse brain membranes. A phosphacan-related chondroitin sulfate proteoglycan.

We have isolated a chondroitin sulfate proteoglycan from mouse brain by affinity chromatography with a fragment of the extracellular matrix glycoprotein tenascin-R (TN-R) that comprises the amino-terminal cysteine-rich stretch and the 4.5 epidermal growth factor-like repeats. The isolated chondroitin sulfate proteoglycan has a molecular mass of 500-600 kDa and carries the HNK-1 carbohydrate epitope. Treatment with chondroitinase ABC reveals a major band of approximately 400 kDa and two minor bands at 200 and 150 kDa. Immunoblot analysis relates the molecule to phosphacan but not to the chondroitin sulfate proteoglycans neurocan and versican. Binding of the phosphacan-related molecule to the epidermal growth factor-like repeats of TN-R is Ca2+-dependent. Co-localization of the molecule with TN-R in the retina and optic nerve by immunocytochemistry suggests a functional relationship between the two molecules in vivo. Inhibition of neurite outgrowth from hippocampal neurons by the phosphacan-related molecule in vitro is neutralized by TN-R when coated as a uniform substrate. Furthermore, the phosphacan-related molecule neutralizes growth cone repulsion induced by TN-R coated as a sharp substrate boundary with or without prior treatment with chondroitinase ABC. These observations indicate that TN-R can interact with a phosphacan-related molecule and thereby modulate its inhibitory influence on neuritogenesis.

Animals↗